Previous studies have established that axon sprouting in deafferented brain areas of the adult brain is greatly reduced from that found after comparable lesions in neonates. Experiments using rat hippocampus have shown that the limitations observed by the mature form of sprouting are correlated temporally with a series of reactive changes in glial cells and spatially with the distribution of persistent degeneration products. The proposed experiments will attempt to test correlations by measuring the time course and extent of sprouting under conditions in which the numbers of these astrocytes, oligodendroglia, and myelinated fibers have been greatly reduced. The first project is intended to find injection dosages of the drug 6-aminonicotinamide which are selectively cytotoxic for astroglia in hippocampus. The second study will determine if the mutant mouse "Jimpy" is lacking in oligodendroglia and myelinated axons in hippocampus as has been reported for other brain areas. Sprouting in these preparations will then be evaluated using fiber stains and anterograde transport techniques.